WO1998056768A1 - Tricyclic pyrrole or pyrazole derivatives - Google Patents

Abstract

Tricyclic pyrrole or pyrazole derivatives represented by general formula (I) or pharmaceutically acceptable salts thereof, which have high selectivity and affinity for 5-HT2c receptors and are useful in treating central nervous system diseases such as sexual function disorder, appetite regulation disorder, anxiety, depression or sleep disturbance. In said formula, the ring Y represents an unsaturated 5-membered ring optionally having 1 to 3 heteroatoms of one or more types selected from the group consisting of nitrogen, oxygen and sulfur or an unsaturated 6-membered ring having 1 or 2 nitrogen atoms; X represents a bond or carbon; --- represents a double or single bond; V represents nitrogen or CH; and A represents linear or branched lower alkylene optionally substituted by halogeno or cycloalkyl.

Description

 Specification

 Tricyclic pyrrol or pyrazole derivatives

 The present invention relates to a novel tricyclic pyrrol or pyrazole derivative or a pharmaceutically acceptable salt thereof. The present invention also relates to a pharmaceutical composition comprising the tricyclic pyrrole or pyrazole derivative or a salt thereof and a pharmaceutically acceptable carrier, particularly a central nervous system disease, for example, sexual dysfunction, appetite regulation The present invention relates to a pharmaceutical composition useful as an agent for preventing and treating disorders, anxiety, depression, and sleep disorders. Background art

 With the advent of an aging society, the improvement and improvement of the lives of the elderly has been reviewed, and focus has been placed on prevention or treatment of diseases that have been given up as non-diseases such as sexual dysfunction. It has come to be.

5—HT _2C receptors are mainly centrally distributed and their role is poorly understood, but central nervous system disorders such as sexual dysfunction, anorexia, anxiety, depression, sleep disorders Invest. Drugs 2 (4) 317 (1993)). Therefore, 5-HT _2C receptor agonists are useful for the prevention or treatment of the above-mentioned diseases, and especially useful for diseases for which there is no effective treatment method that has been abandoned as a disease such as sexual dysfunction. it is conceivable that.

5 -HT is a ₂ c is a receptor agonist tricyclic pyrrole or pyrazole Ichiru derivatives, tricyclic pyrrole derivatives benzene rings are condensed (EP 657426- A)及beauty benzene rings condensed tricyclic Pyrazole derivatives (EP 700905-A) have been reported.

International Publication W096 / 13478 discloses a tricyclic pyrrole or pyrazole derivative in which a pyrazine ring, a pyridine ring, a thiophene ring, a furan ring or a pyrrole ring, which is a retinoide antagonist, is described.W095 / 07893 discloses dopamine. Receptor has a tricyclic pyrazole or birazol skeleton with an aromatic ring fused to an aromatic ligand, and has a substituent at a carbon atom of the pyrrole or pyrazole ring in the skeleton. Compounds have been reported. Disclosure of the invention

 The present inventors have conducted intensive studies on a previously unknown tricyclic pyrrole or pyrazole derivative in which an amino group is bonded to the 1-position via an alkylene chain and an unsaturated heterocyclic ring is condensed. As a result, a novel tricyclic pyrazole or birazol derivative is

The inventors have found that they have high selectivity and affinity for 5-HT _{2 C} receptor, and have completed the present invention.

That is, the present invention provides a novel tricyclic pyrrole or pyrazole derivative represented by the following general formula (I) showing high selectivity and affinity for 5-HT _{2 C} receptor, or a pharmaceutically acceptable salt thereof. About.

 (The symbols in the formula have the following meanings

Y ring: an unsaturated 5-membered ring which may have 1 to 3 or 1 or 3 or more hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, or 1 to 2 nitrogen atoms Unsaturated 6-membered ring

X: bond or carbon atom

-: Double bond or single bond

V: a nitrogen atom or a group represented by the formula CH

 A: A linear or branched lower alkylene group which may be substituted with a halogen atom or a cycloalkyl group

R ¹ and R ^2: the same or different and represent a hydrogen atom, a lower alkyl group or R ¹ and R ² or A is may be formed hetero ring together with the adjacent nitrogen atom a nitrogen-containing saturated R ³ and R ⁴ : Same or different hydrogen atom, lower alkyl group, hydroxyl group, lower alcohol Xy group, amino group, mono- or di-lower alkylamino group, lower alkanoylamino group or halogen atom

R ^{5 to} R ⁹ : the same or different, a hydrogen atom, a lower alkyl group, a hydroxyl group or a lower alkoxy group

However, when 7777: is a double bond, R ⁶ and R ⁸ do not exist. Also, when X is a bond, 7777 is a single bond and R ⁷ and R ⁸ are absent. )

 The compound (I) of the present invention has a chemical structure in which an amine is always bonded via an alkylene chain to the 1-position of a tricyclic pyrrole or virazole skeleton to which an unsaturated heterocycle is fused. There are features.

The present invention is preferably

A compound of the present invention (A) wherein A is an ethylene or propylene group, and more preferably a compound of the present invention (I) wherein the Y ring is a furan or thiophene ring; Particularly preferred is 2- (1-furo [2,3-g] indazo-l-l-^-l) ethylamine, 2- (7-promo 1 thieno [2,3-g] indazol-l-yl ) Ethiluamine, 2- (7-odo 1 H-thieno [2,3-g] indazolyl-1 ^^ T) ethyluamine, 2- (7-methoxy-1 H-thieno [2,3-g ] Indazoyl 1-yl) ethylamine, (S) — 2— (1H—furo [2,3-g] indazole—11-yl) 1-1-methylethylamine, 2 -— (7— Methyl-1 fi-thieno [2,3-g] indazole-1-11) ethylamine, (S) -2- (7-methoxy-1-dithieno [2,3-g] indazole 1 —yl) 1-methylethylamine, (S) — 1-methyl-2- (7-methyl_1H-thieno [2,3-g] indazo 1-yl) ethylamine, 2— (7-ethyl-1 ff-thieno [2,3-g] indazo 1-yl) ethylilamine, (S) -2- (7-ethyl-1ff-thieno [2,3-g] indazo-1 L-yl)-1-methylethylamine or a pharmaceutically acceptable salt thereof. Further, the present invention provides a pharmaceutical composition comprising a tricyclic pyrrole or pyrazole derivative represented by the general formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Preferably, a pharmaceutical composition having high selectivity and affinity for 5-HT _{2 C} receptor, more preferably, sexual dysfunction such as impotence, appetite regulation disorder such as obesity, bulimia or anorexia nervosa, and anxiety It is an object of the present invention to provide a pharmaceutical composition which is a therapeutic agent for central nervous system diseases such as depression or sleep disorder, and particularly preferably a pharmaceutical composition which is a therapeutic agent for sexual dysfunction such as impotence.

 Hereinafter, the compound (I) of the present invention will be described in detail.

A “5-HT _{2 C} receptor agonist” is a compound that has an affinity for 5-HT _{2 C} receptor and has an agonistic or antagonistic action.

 In the definition of the general formula in the present specification, unless otherwise specified, the term “lower” means a straight or branched carbon chain having 1 to 6 carbon atoms.

 As the "lower alkylene group", specifically, for example, methylene, ethylene, trimethylene, propylene, tetramethylene, ethylethylene, pentamethylene, hexamethylene group and the like can be mentioned, and an ethylene group and a propylene group are preferable.

 Specific examples of the “lower alkyl group” include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl (amyl), isopentyl, neopentyl, tert-pentyl, hexyl, Examples include an isohexyl group and the like, preferably an alkyl group having 1 to 4 carbon atoms, and particularly preferably a methyl group.

 “Cycloalkyl group” means a monocyclic hydrocarbon ring group having 3 to 8 ring atoms, and specifically includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. And preferably a cyclohexyl group.

 The “lower alkoxy group” means an oxy group substituted by the lower alkyl group.

 The “mono- or di-lower alkylamino group” means an amino group in which the above lower alkyl group is substituted by 1 or 2 groups.

"Lower alkanoylamino" means a hydrogen atom or a lower alkyl group described above. Means a radical ponylamino group.

 The “halogen atom” includes a fluorine, chlorine, bromine or iodine atom, and is preferably a chlorine, bromine or iodine atom.

 `` Unsaturated 5-membered ring which may have 1 to 3 or 1 or 2 or more hetero atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom '' Pentene, pentoxen, thiophene, furan, pyrrol, imidazole, pyrazol, thiazole, oxazole, isothiazole, isoxazole, triazole, thiadiazol, oxaziazole and the like, preferably thiophene and furan. is there.

 The “unsaturated 6-membered ring having 1 or 2 nitrogen atoms” specifically includes, for example, pyridine, pyridazine, pyrimidine, pyrazine and the like, and is preferably pyridine.

 “Nitrogen-containing saturated heterocycle” means a 3- to 8-membered nitrogen-containing saturated heterocycle, specifically, for example, aziridine, azetidine, pyrrolidine, piperidine, hexahydroazepine, or oxhydroazazocin. And pyrrolidine and piberidine are preferred.

 The compound (I) of the present invention may have an asymmetric carbon atom depending on the type of the substituent. Therefore, the compound (I) of the present invention includes a mixture of optical isomers and an isolated one.

 The compound (I) of the present invention can form an acid addition salt. The compounds of the present invention also include these salts. Specific examples of such salts include inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid, formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, and the like. Organic acid acids such as fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; and acid addition salts with acidic amino acids such as aspartic acid and glumic acid.

 Furthermore, the compound (I) of the present invention or a pharmaceutically acceptable salt thereof can be isolated as various solvates such as hydrates and ethanol solvates or as polymorphic substances thereof. In some cases, the compounds of the present invention also include various hydrates, solvates and polymorphic substances.

(Manufacturing method) The compound (I) of the present invention can be produced by applying various synthetic methods utilizing characteristics based on the basic skeleton or the type of the substituent. Hereinafter, a typical manufacturing method will be described.

First manufacturing method

(In the formula, ¹ to ⁹ , V, X, Y, and Α are as described above, and Z means a leaving group such as a halogen atom, a tosyloxy group, and a mesyloxy group.)

 The compound (I) of the present invention can be produced by reacting a compound represented by the general formula (II) with an appropriate amine to convert the compound into a corresponding amino compound.

 This reaction can be carried out in the presence or absence of a suitable solvent, in the presence of a suitable base if necessary, under cooling or heating, or, if necessary, in a sealed reaction vessel.

Second manufacturing method

^{(Wherein, R 3 ~ 9, V,} X, Υ, Γττ the ^ and Α are as previously described, D is meant one less alkylene group with a carbon number of from A.)

 The compound (I) of the present invention can be produced by reducing a nitrile compound represented by the general formula (III).

This reaction is carried out in the presence or absence of a suitable inert solvent such as getyl ether, t-butyl methyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, methylene chloride, benzene or toluene, preferably Such as tetrahydrofuran The reaction can be carried out in ethers, if necessary, in the presence of a suitable Lewis acid, using a suitable reducing agent, under cooling or heating, preferably at room temperature. As the Lewis acid, a salt amide solution or the like can be used, and as the reducing agent, a hydride complex such as lithium aluminum hydride or the like can be used. In this reaction, an appropriate solvent such as ethyl acetate, alcohol, tetrahydrofuran, dioxane, acetic acid or a mixture thereof is used on a metal catalyst, preferably a palladium-carbon catalyst, platinum oxide, Raney nickel or the like. It can also be carried out by catalytic hydrogenation.

Third manufacturing method

^{(Wherein, R 3 ~ 9, V,} X, Y,及A is as described above, E is § disilazide group, a nitro group, an amino group, such as normal Amino group protected with a protecting group to be used It means a group that can be easily converted.A and E may be combined with each other to form a nitrogen-containing saturated heterocycle.)

 The compound (I) of the present invention can also be produced by reducing the compound represented by the general formula (IV) or removing the protecting group.

 When E represents an azide group or the like, this reduction reaction is carried out in the presence or absence of a suitable inert solvent similar to that used in the second production method, preferably in ethers such as tetrahydrofuran. If necessary, the reaction can be carried out under cooling or heating, preferably at room temperature, using a suitable reducing agent in the presence of a suitable Lewis acid such as aluminum chloride. As the reducing agent, a hydride complex such as lithium aluminum hydride or the like can be used. In this reaction, an appropriate solvent such as ethyl acetate, alcohol, tetrahydrofuran, dioxane, acetic acid or a mixture thereof is used on a metal catalyst, preferably a palladium carbon catalyst, platinum oxide, Raney nickel or the like. It can also be carried out by catalytic hydrogenation or by using triphenylphosphine.

When E represents a nitro group or the like, the present reduction reaction is carried out in a suitable solvent, for example, ethyl acetate, The reaction can be carried out by catalytic hydrogenation on a metal catalyst using alcohol, tetrahydrofuran, dioxane, acetic acid or a mixture thereof. Alternatively, the reaction can be carried out in the presence or absence of a suitable solvent, by using a metal (eg, iron, tin) or the like, in the presence of an acid catalyst, and under cooling or heating.

 When E represents an amino group or the like protected with a commonly used protecting group, it can be converted into an amino group by deprotection according to a conventional method. For example, when the protecting group is a fluoroimide group or an acetoamide group, a similar method described in Protecting Groups in Organic Synthesis, John Wiley & Sons, INC. Can be used. If it is a ponyl group, a conventional reduction reaction can be used.

4th manufacturing method

 1-9

 (In the formula, R V, X, Y, and Α are as described above.)

 The compound (I) of the present invention can be produced by N-alkylation of the compound represented by the general formula (Ia) produced by the second and third production methods.

 This reaction is carried out in the presence or absence of a suitable solvent, in the presence of a suitable alkylating agent, preferably a lower alkyl halide (eg, propyl iodide), and if necessary, a suitable base as a deoxidizing agent, and then cooling or heating. Can be done below.

 A reductive alkylation reaction can also be performed as the present alkylation reaction. Using a reducing agent such as a borohydride reagent (eg, sodium triacetoxyborohydride) in the presence or absence of a suitable inert solvent, if necessary, in the presence of an acid catalyst, preferably an inorganic acid or an organic acid, An appropriate lower alkyl aldehyde (for example, propanal) can be reacted under cooling or heating.

The starting compounds of the first and second production methods can be easily obtained by the methods of Reference Examples and Examples described below, or according to or by applying the methods of Reference Examples and Examples. The compound of the present invention thus produced is isolated as it is or as a salt thereof. The salt of the compound of the present invention can be produced by subjecting the compound of the present invention, which is a free base, to a conventional salt-forming reaction.

 The compound (I) of the present invention or a salt thereof is isolated and purified as a hydrate, solvate, or polymorphic substance thereof. Isolation and purification are performed by applying ordinary chemical operations such as extraction, concentration, distillation, crystallization, filtration, recrystallization, and various types of chromatography. Various isomers can be separated by selecting an appropriate starting compound or by utilizing a difference in physical properties between the isomers. For example, the optical isomer can be obtained by selecting an appropriate raw material, or by a racemic resolution method of a racemic compound (for example, a method of leading to a diastereomer monosalt with a general optically active acid and performing optical resolution). It can lead to chemically pure isomers.

 Hereinafter, in addition to those described in the examples, the above-mentioned production methods, the production methods of the examples and reference examples, ordinary production methods known to those skilled in the art, and modifications thereof are required, and special experiments are required. The following compound can be obtained without using:

 2- (6-Methoxy-1-thieno [3,4-g] indazo-l-l-l-^-l) ethylamine; 2- (lfi-pyrazo-mouth [3,4-e] [1,2] benzisothiazo-l Le — 1 _yl) ethylamine; 2— (l / ί—pyrazo [3,4-d] benzofurazan — 1-yl) ethylamine; 2—pyrazo [3,4-d] 1-2,1, 3—Benzothiadiazoyl 1-yl) ethylamine; 2— (7-methoxy-1H, 6—pyro [2,3-g] indazoyl 1-yl) ethylamine; 2 -— (1H, 6H —Pyrazo mouth [3,4-e] benzimidazoyl—11-yl) ethylamine; 2- (1H, 6 —Pyrazo-mouth [3,4-e] benzotriazo-1-yl) ethyl ethylamine Possibility of using

The compound of the present invention has high selectivity and affinity for the 5-HT _2e receptor and is also effective in animal experiments. Therefore, central nervous system diseases such as sexual dysfunction such as impotence, obesity, It is useful for treating appetite dysregulation such as bulimia or anorexia nervosa, anxiety, depression and sleep disorders. The selectivity and affinity of the compound of the present invention for 5-HT _2C receptor and the evaluation by animal experiments using rats were confirmed by the following methods.

 A. Combination experiment

5 -HT _{2 c} and 5-HT _{2 A} receptor:.... A. Pazos et al, Eur J. Pharmacol, 106, 539-546 (1985) or, S. havlik and SJ Peroutka, Brain Res, 584 , 191-196 (1992)

[ ³ H] 5-HT binding analysis was performed.

Using the above method obtains the drug concentration which inhibits 50% of the receptor binding ligand (IC _5Q value), K i values representing the affinity for the receptor is converted by the following formula: K i = IC _{5 0} Z (1+ [L] Z [Kd]) ([L]: ligand concentration, [Kd]: dissociation constant) The results are shown in Table 1.

 Table 1 Binding experiments (K i, nM)

As described above, the compound of the present invention has a high affinity for the 5-HT _2C receptor and has a ten-fold or higher selectivity for the 5-HT _2A receptor.

B. Animal experiments using rats

Rat penile erection-inducing action: It is known to induce penile erection by 5-HT _2C receptor stimulation (Berendsen & Broekkamp, Eur. J. Pharmacol., 135, 179-184 (1987)). The test compound was administered to rats, and immediately after the administration, the number of penile erections for 30 minutes was measured to determine the minimum effective dose at which a statistically significant response was observed.

 As a result, it was found that the compounds of the present invention exhibited strong activity with a minimum effective dose of 0.003 to 1 mg / kg, sc.

As described above, the compound of the present invention is effective in animal experiments using rats, and is therefore useful for treating central nervous system diseases, for example, for treating sexual dysfunction such as impotence. Pharmaceutical compositions containing one or more of the compound (I) of the present invention, a pharmaceutically acceptable salt thereof, a hydrate thereof, a solvate thereof and the like as an active ingredient are usually used for formulation. Tablets, powders, fine granules, granules, capsules, pills, solutions, injections, suppositories, ointments, patches, etc. It is administered orally (including sublingual administration) or parenterally.

 The clinical dose of the compound (I) of the present invention to humans is appropriately determined depending on the individual case in consideration of the patient's symptoms, weight, age, sex, administration route, etc. Orally administered once or several times daily in the range of 10 mg to 1000 mg, preferably 50 mg to 20 mg per day, or 1 mg to 50 mg, preferably 5 mg to 10 mg per day per adult Intravenous administration in the range of Omg once a day to several times a day or continuous intravenous administration in the range of 1 hour to 24 hours a day. Of course, as described above, since the dose varies under various conditions, a smaller dose than the above dose may be sufficient.

 As the solid composition for oral administration according to the present invention, tablets, powders, granules and the like are used. In such solid compositions, the one or more active substances include at least one inert diluent, such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, metasilicone. It is mixed with magnesium acid aluminate. In accordance with the usual methods, the composition may contain additives other than inert diluents, such as lubricants such as magnesium stearate, disintegrants such as calcium cellulose glycolate, stabilizers such as lactose, glutamine. A solubilizing agent such as an acid or aspartic acid may be contained. The tablets or pills may be coated with sugar coating such as sucrose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate or the like, or with a gastric or enteric film, if necessary.

 Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like, and commonly used inert diluents such as purified Contains water and ethanol. The composition may contain, in addition to the inert diluent, solubilizing or solubilizing agents, wetting agents, auxiliary agents such as suspending agents, sweetening agents, flavoring agents, fragrances, and preservatives.

Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Aqueous solutions and suspensions include, for example, distilled water for injections and neat Contains saline. Examples of the water-insoluble solutions and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, and polysorbate 80 (trade name). Such compositions may further comprise additives such as tonicity agents, preservatives, wetting agents, emulsifiers, dispersants, stabilizers (eg, lactose), solubilizing or solubilizing agents. These are sterilized by, for example, filtration through a bacteria retaining filter, blending of a bactericide or irradiation. These can also be used by producing a sterile solid composition and dissolving it in sterile water or a sterile injection solvent before use. BEST MODE FOR CARRYING OUT THE INVENTION

 Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. The starting compounds used in the examples will be described as reference examples.

Reference example 1

 Potassium tert-butoxide 2.95 g of tetrahydrofuran (20 ml) solution Under ice-cooling 4-oxo-1,4,5,6,7-tetrahydrobenzo [b] thiophene 2.00 g and ethyl formate 3.89 g of tetrahydrofuran (10 ml) The solution was added dropwise and stirred at room temperature for 30 minutes. After adding 26 ml of 1N hydrochloric acid to the reaction solution, 3.16 g of hydrazinoethanol was added thereto under ice cooling, followed by stirring at room temperature for 2 hours. After the reaction solution was extracted with methylene chloride, the organic layers were combined, washed with brine, and dried over anhydrous magnesium sulfate. After filtering off the desiccant, the filtrate was concentrated under reduced pressure to give 2- (4,5-dihydro-thieno [2,3-g] indazole-1-yl) ethanol 1.56 as a pale yellow solid.

 In the same manner as in Reference Example 1, Reference Example 2 and 20 compounds were obtained.

Reference Example 2: 2- (1,4-dihydrocheno [3 ', 2': 4,5] cyclopentyl [1,2-c] pyrazole-11-yl) ethanol

Reference Example 3: 2- (4,5-dihydro-1 fi-furo [2,3-g] indazole-1 fle) Ethanol

Reference Example 4: 2- (4,5-dihydro-1ίί-furo [3,2-g] indazole_1 11) ethanol Reference Example 5: 2- (4,4-dimethyl-4,5-dihydrofuro [2,3-g] indazole-1yl) ethanol

Reference Example 6: 2- (1,4-dihydrocheno [2 ', 3': 4,5] cyclopentene

 [1,2-c] pyrazole-yl) ethanol

Reference Example 7: 2- (7-Bromo_4,5-dihydro-1thieno [2,3-g] indazo-1-yl 1-yl) ethanol

Reference Example 8: 2- (7-odo-4,5-dihydro-1if-thieno [2,3-g] indazo-l-yl) ethanol

Reference Example 9: 2- (7-chloro-4,5-dihydro-1 fithieno [2,3-g] indazol-1yl) ethanol

Reference Example 10: 2- (7-Methoxy-4,5-dihydro-1H-thieno [2,3-g] indazol-1-yl) ethanol

Reference Example 1 1: 2_ (8-Methyl-4,5-dihydro-1 fi-pyrazo mouth [3,4-e] [1,2] Benzisoxazole _ 1-yl) Ethanol

Reference Example 12: 2- (7-Methyl-4,5-dihydro-1H-pyrazo-mouth [3,4-e] benzothiazol-1-yl) ethanol

Reference Example 13: 7-Edo-4,5-dihydro-1 thieno [2,3-g] indazole

Reference Example 14: 7-Bromo-4,5-dihydro-1thieno [2,3-g] indazole.

Reference Example 15: 2- (7-methyl-4,5-dihydro-1H-thieno [2,3-g] indazole-1-yl) ethanol

Reference Example 16: 7-Ethyl-4,5-dihydro-1 thieno [2,3-g] indazole

Reference Example 17: 2- (7-Methyl-4,5-dihydro-1H-furo [2,3-g] indazol-11-yl) ethanol

Reference Example 18: 7-Methyl-4,5-dihydro-1 flow [2,3-g] indazole

Reference Example 19: 7-Isopropyl-1,4,5-dihydro-1H-thieno [2,3-g] -Le

Reference Example 20: 2- (7-Ethoxy_4,5-dihydro_1H-thieno [2,3-g] indazol-1-1) ethanol

Reference Example 21

 2- (1,4-dihydrothieno [2 ', 3': 4,5] cyclopentyl [1,2-c] pyrazol-1-yl) Dissolve 0.50 g of ethanol in 15 ml of methylene chloride Then, 1.00 ml of triethylamine and 0.28 ml of methanesulfonyl chloride were added thereto, and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into ice water and extracted with black-mouthed form. The organic layers were combined, washed with a saturated saline solution, and dried over anhydrous magnesium sulfate. After filtering off the desiccant, concentrate under reduced pressure and concentrate under reduced pressure. 2- (1,4-Dihydrocheno [2,3,4 ': 4,5] cyclobenzene [1,2-c] pyrazole- 1 一 1）) ethyl methanesulfo 0.75 g of naat was obtained.

 In the same manner as in Reference Example 21, the compounds of Reference Examples 22 to 28 were obtained.

Reference Example 22: 2- (1,4-dihydrocheno [3,, 2,: 4,5]

 [1,2-c] pyrazol-1-yl) ethyl methanesulfonate

Reference Example 23: 2- (4, 5-dihydro-1-fluoro [2, 3-g] indazole

1-yl) ethyl methanesulfonate

Reference Example 24: 2- (4,4-dimethyl-4,5-dihydro-1if-furo [2,3-g] indazol-1-yl) ethyl methanesulfonate

Reference Example 25: 2— (1H—Flo [2,3—g] Indazo 1 ル ー 1 一 1Γ2）) — 1-Methylethyl methanesulfonate

Reference Example 26: l _ (lfi-flow [2,3-g] indazole-1-ylmethyl) butyl methanesulfonate

Reference Example 27: 1 _ (1H-furo [2,3-g] indazole-1 ^^-methyl)-2-methylpropyl methanesulfonate

Reference Example 28: 1-Cyclohexyl-2- (l-furo [2,3-g] indazole-1 1-yl) ethyl methanesulfonate

Reference Example 29

2-(1, 4-dihydrocheno [2,, 3 ': 4, 5] cyclopentene [1, 2— c] Pyrazol-1-yl) ethyl 0.77 g of methanesulfonate was dissolved in 10 ml of dimethylformamide, 0.47 g of sodium azide was added, and the mixture was stirred at 70 for 17 hours. After cooling, the reaction mixture was poured into ice water and extracted with ether. The organic layers were combined, washed with saturated saline, and dried over anhydrous magnesium sulfate. After the desiccant was removed by filtration, the solvent was concentrated under reduced pressure, and 0.56 g of 1- (2-azidoethyl) -1,4-dihydrocheno [2 ', 3,: 4,5] cyclopentyl [1,2_c] pyrazole was added. Obtained.

 The compounds of Reference Examples 30 to 34 were obtained in the same manner as in Reference Example 29.

Reference Example 30: 1- (2-azidoethyl)-1,4-dihydrocheno [3 ', 2,: 4,5] cyclopentene [1,2-c] pyrazol

Reference Example 31: 1— (2-azidoethyl) -4,5-dihydro-1-furo [2,3-g] indazole

Reference Example 32: 1- (2-azidoethyl) -1,4,4-dimethyl-4,5-dihydro-lfi-furo [2,3-g] indazole

Reference Example 33: 1— (2-azidopropyl) —1H-Flo [2,3—g] indazole

Reference Example 34: 1— (2-azido-2-cyclohexylethyl) — 1H—flow [2,

3—g] indazole

 The compounds of Reference Examples 35 to 59 were obtained in the same manner as in Reference Examples 21 and 29. Reference Example 35: 1- (2-azidoethyl) -4,5-dihydro-1furo [3,21 g] indazole

Reference Example 36: 1- (2-azidoethyl) -7-bromo-4,5-dihydro-1H-thieno [2,3-g] indazole

Reference Example 37: 1- (2-azidoethyl) -7-odo-4,5-dihydro-in-thieno [2,3-g] indazole

Reference Example 38: 1- (2-azidoethyl) -17-chloro-4,5-dihydro-1H-thieno [2,3-g] indazole

Reference Example 39: 1- (2-azidoethyl) — 7-methoxy-4,5-dihydro-1H-thieno [2,3-g] indazole

Reference Example 40: 1- (2-Azidobutyl) fluoro [2,3-g] indazole Reference Example 41: 1- (2-azidoethyl) -8-methyl-4,5-dihydro-ΙΙί-pyrazo mouth [3,4-e] [1,2] benzisoxazole

Reference Example 42: 1- (2_Azidoethyl) -17-methyl-4,5-dihydro-1 fi_ pyrazo mouth [3,4-e] benzothiazole

Reference Example 43: 1- (2-azidoethyl) -1,4,5-dihydro-1H-cheno [2,3-g] indazole

Reference Example 44: (S) — 1— (2-azidopropyl) _ 1 H—pyrazo mouth [3, 4—e] benzoxazole

Reference Example 45: (S) -1-(2-Azidopropyl) — 7-methyl-1 1-pyrazo mouth

 [3, 4-e] benzoxazole

Reference Example 46: (S) — 1— (2-azidopropyl) 1-1H—thieno [2,3-g] indazole

Reference Example 47: (S) -1-(2-azidopropyl) 1 7-promo 1 fi-thieno [2,3-g] indazole

Reference Example 48: (S) -1-(2-Azidopropyl) 1 7-Anode-1H-thieno [2,3-g] indazole

Reference Example 49: (S)-1-(2-azidopropyl)-7-chloro-1-thieno [2,3-g] indazole

Reference Example 50: 1- (2-azidoethyl) -17-methyl-4,5-dihydro-1H-thieno [2,3-g] indazole

Reference Example 51: (S) -1- (2-azidopropyl) -1-7-methyl-1H-thieno [2,3-g] indazole

Reference Example 52: (S) -1- (2-azidopropyl) -1-7-ethyl-1 thieno [2,3-g] indazole

Reference Example 53: (S) -1-(2-azidopropyl) 1 7-methyl-1 flow [2,3-g] indazole

Reference Example 54: (S) -1- (2-azidopropyl) -17-isopropyl-1-H-thieno [2,3-g] indazole

Reference Example 55: 1- (2-azidoethyl) -7-ethoxy-4,5-dihydro- —Thieno [2,3— g] indazole

Reference Example 56: (S) 1-11 (2-azidopropyl) — 3-ethyl — 1 fi-flow [2,3-g] indazole

Reference Example 57: (S) -1- (2-azidopropyl) -1-3-propyl-1H-furo [2,3-g] indazole

Reference Example 58: (S)-1-(2-azidopropyl)-3-methoxy-1 fi-flow [2, 3-g] indazole

Reference Example 59: 1- (2-azidocyclohexyl) -1H-furo [2,3-g] indazole

Reference Example 60

 1- (2-azidoethyl) _4,5-dihydro-1-thieno [2,3-g] -indazole 1.00 g is dissolved in dioxane 3 Om 1 and 2,3-dichloro-5,6 2.8 g of _____________________________________ DIANO 1,4-benzoquinone was added at room temperature, and it heated and refluxed for 8 hours. After cooling, the reaction solution was poured into an aqueous solution of sodium hydrogen carbonate and extracted using a black hole form. The organic layers were combined and dried over anhydrous magnesium sulfate. After the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. Obtained as a product.

 The compounds of Reference Examples 61 to 74 were obtained in the same manner as in Reference Example 60.

Reference Example 6 1: 1- (2-azidoethyl) — 7-promo — 1 H-thieno [2,3-g] indazole

Reference Example 62: 1-(2-azidoethyl) — 7-iodo 1 fi-thieno [2,3-g] indazole

Reference Example 63: 1-(2-azidoethyl) — 8-methyl — lfi — pyrazo mouth [3, 41 e] [1, 2] benzisoxazole

Reference Example 64: 1- (2-azidoethyl) -7-methyl-1H-pyrazo-mouth [3,4-e] benzothiazol

Reference Example 65: 7—Ed—1 if—Thieno [2,3—g] Indazole

Reference Example 66: 7-Bromo-1 fi-thieno [2,3_g] indazole Reference Example 67: 7-cloth — 1 thieno [2,3-g] indazole Reference Example 68: 1- (2-azidoethyl) 1 7-methyl-1H-thieno [2,3_g] indazole

Reference Example 69: 7-Methyl-1 f-thieno [2,3-g] indazole

Reference example 70: 7-ethyl 1-thieno [2,3-g] indazole

Reference Example 7 1: 7-Methyl-Iff-Flo [2,3-g] indazole

Reference Example 72: 7-Isopropyl_1 if-thieno [2,3-g] indazole Reference Example 73: 1- (2_azidoethyl) -17-ethoxy-1H-thieno [2,3-g] indazole

Reference Example 74: N- [2- (1H-furo [2,3-g] indazole-1-yl) ethyl] acetamide

 The compounds of Reference Examples 75 and 76 were obtained in the same manner as in Reference Examples 1 and 60. Reference Example 75: 7-Methoxy-1H-thieno [2,3-g] indazole

Reference Example 76: 7-tert-butyl-1 1-thieno [2,3-g] indazole

 The compounds of Reference Examples 77 and 78 were obtained by a conventional acetylation reaction.

Reference Example 77: N— [2— (4,5-dihydro-1 fi-furo [2,3—g] indazo-1-ru-1) ethyl] acetoamide

Reference Example 78: N— [2— (4,5-dihydro-1H—furo [3,2—g] indazo—Ru-1-yl) ethyl] acetamide

Reference Example 79

 Under an argon stream, 0.72 g of sodium hydride was added with 15 ml of dimethylformamide, and 1 H-furo [2,3-g] indazole 2 obtained in the same manner as in Reference Examples 1 and 60 was added thereto. A solution of 60 g of dimethylformamide (10 ml) was added dropwise, and the mixture was stirred for 30 minutes. Further, 2.10 ml of ethyl bromoacetate was added to the reaction solution under ice cooling, and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layers were combined, washed with saturated saline, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography to obtain 2.70 g of ethyl acetate (lJi-Flo [2,3-g] indazole-1-yl).

Reference Example 80 Under an argon stream, 0.44 g of lithium aluminum hydride was suspended in 50 ml of tetrahydrofuran, and 2.60 g of (l fi-furo [2,3-g] indazole-1-yl) ethyl acetate was added thereto. Of tetrahydrofuran (10 ml) was added dropwise, and the mixture was stirred at room temperature for 1 hour. Methanol was added to the reaction mixture under ice-cooling to decompose excess lithium aluminum hydride, and then 0.44 m of water and 0.44 m of a 15% aqueous sodium hydroxide solution were added. After stirring at room temperature for 30 minutes, anhydrous magnesium sulfate and celite were added, and the mixture was further stirred for 30 minutes. The insolubles were removed by filtration through celite, and the filtrate was concentrated under reduced pressure to obtain 1.82 g of 2- (Iff-flow [2,3-g] indazole-1yl) ether.

Reference Example 8 1

2- (Iff-Flo [2,3_g] indazole-1yl) Ethanol 1.80 g of dimethylsulfoxide (15 ml) solution in triethylamine 4.20m 1 and S ₃ -pyridine complex 4 A solution of 74 g of dimethyl sulfoxide (15 ml) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was poured into water, acidified with 1N hydrochloric acid, and extracted with ethyl acetate. The organic layers were combined, washed with saturated saline, and dried over anhydrous magnesium sulfate. After the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give 0.89 g of (1H-furo [2,3-g] indazole-1-yl) acetaldehyde. Obtained.

Reference Example 8 2

 In an argon stream, 0.27 g of sodium hydride was added to a solution of dimethylformamide (10 ml) in l fi-flow [2,3-g] indazole. 1. OO g of a solution of dimethylformamide (5 ml) was added. The mixture was dropped on ice and stirred for 30 minutes. Further, 0.52 ml of propylene oxide was added to the reaction solution under ice cooling, and the mixture was stirred at room temperature for 41 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layers were combined, washed with a saturated saline solution, and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography, and 1- (Iff-furo [2,3-g] indazole-1 l-pyrole) propane-2-ol 0.59 g I got

 In the same manner as in Reference Example 82, the compounds of Reference Examples 83 and 97 were obtained.

Reference Example 83: (R) -1-Pyrazo mouth [3, 4-e] Benzoxazo 1-yl) —2-propanol

Reference Example 84: (?) — 1— (7-Methyl _ 1 pyrazo mouth [3, 4—e] benzoxaxazo 1-ru 1-yl) 1 2-propanol

Reference example 85: (i?) _ 1— (1 fi—thieno [2, 3— g] indazole _ 1 _yl) ― 2—propanol

Reference Example 86: (R) — 1— (7 _bromo-1 1thieno [2,3—g] indazole — 1-yl) —2-propanol

Reference Example 87: (i?) _ 1— (7-node-1 if—thieno [2,3-g] indazole—one-one) 2-propanol

Reference Example 88: (i?) _ 1 _ (7-black mouth-1 ίί-thieno [2,3-g] indazo 1-yl) —2-propanol

Reference Example 89: (i?) — 1 _ (7-methyl-1H-thieno [2,3-g] indazol—11-yl) _2-propanol

Reference Example 90: (R) — 1— (7_ethyl—1 fi—thieno [2,3—g] indazole—11-yl) —2-propanol

Reference Example 91: (i?) _ 1- (7-methyl-1H-furo [2,3-g] indazol-1 fl) _ 2-propanol

Reference Example 92: (i?) — 1— (7_isopropyl-1- 1ff-thieno [2,3_g] indazo-1-yl) 1-2-propanol

Reference Example 93: (i?) — 1— (3-methoxy-1-f-furo [2,3-g] indazole—1-yl) -1-2-propanol

Reference Example 94: (S) -1-furo [2,3—g] indazole—1-yl) —2-propanol

Reference example 95: 1— (1 / —f mouth [2,3—g] indazole_1 mol) 1,3,3,3-trifluoro-2-propanol

Reference Example 96: 1— (1—furo [2,3—g] indazole—11-yl) 1—2-cyclohexanol

Reference Example 97: (i?) — 1— (3-Ethyl _ 1 fi—Flo [2,3—g] Indazol — 1 ^^ Γ) —2—Propanol Reference 98

 By the same method as in Reference Examples 82, 21 and 29, (S) 1 (2-azidopropyl) —— furo [2,3-g] indazole was obtained.

Reference 99

 Under a stream of argon, 5 ml of a 1.0 M solution of ethylmagnesium bromide in tetrahydrofuran was diluted with 5 ml of tetrahydrofuran, and this was diluted with (1H-furo [2,3-g] indazole-1-yl) acetaldehyde. A solution of 30 g of tetrahydrofuran (5 ml) was added dropwise, and the mixture was stirred at room temperature for 3 days. The reaction solution was poured into aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layers were combined, washed with a saturated saline solution, and dried over anhydrous magnesium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography to obtain 0.29 g of 1_ (1H-flow ([2,3-g] indazoyl 11-yl) —2—butanol). Obtained.

 The compounds of Reference Examples 100 to 102 were obtained in the same manner as in Reference Example 99.

Reference Example 100: 1-Flo [2,3-g] indazole-1 -yl) 1-2 Pennol

Reference Example 101: 1— (1 _Flo [2, 3 g] Indazo 1 1 1 ル 1) 1 3 Methyl 2 2

Reference example 102: 1-sh -2-(Iff-Flo [2, 3-g] Indazolu 11-yl) Ethanol

Reference Example 103

The reaction mixture was added to a solution consisting of 1.80 g of 5-aryl-1-oxo 45,6,7-tetrahydrobenzo [b] thiophene, 25 mg of osmium tetroxide, 15 ml of water, and 45 ml of dioxane. While maintaining the temperature at 26 ° C, 4.20 g of sodium periodate was gradually added thereto, followed by stirring at room temperature for 3 hours. After the reaction solution was extracted with ethyl acetate, the organic layers were combined, washed with a 2% aqueous sodium thiosulfate solution, water and brine in that order, and dried over anhydrous magnesium sulfate. After the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give (4-oxo-1,4,5,6,7-tetrahydrobenzo [b] thiophen-5-yl) acetate. 1.33 g of the aldehyde were obtained. Dissolve 1.32 g of the aldehyde and 1.39 g of N-acetylethylenediamine in 50 ml of toluene To the mixture was added 1 Omg of camphorsulfonic acid, and the mixture was refluxed for 3 hours while distilling off generated water. After cooling, the reaction solution was poured into ice-saturated aqueous layer water and extracted with ethyl acetate. The organic layers are combined, the desiccant is removed by filtration, and the mixture is concentrated under reduced pressure. N- [2- (4,5-dihydro-1-thieno [2,3-g] indone-l-yl) ethyl] acetamide 1.38 g I got From this compound, N- [2- (1H-thieno [2,3-g] indo-l-uyl) ethyl] acetoamide was obtained in the same manner as in Reference Example 60.

 The compounds of Reference Examples 104 to 115 were obtained in the same manner as in Reference Example 79.

Reference Example 104: 2- (1H-Flo [2,3-g] indazole-11-yl) propionitrile

Reference Example 105: 2— (1H—Flo [2,3-g] indazol 1-yl)

Reference Example 1 06: 2— (1 _9 ~ Flo [2,3-g] indazol-1-yl)

Reference Example 1 07: 2- (3-ethyl-1H-furo [2,3-g] indazole-1yl) acetonitrile

Reference Example 1 08: 2— (1,5,6,7-tetrahydrocyclopentene [f] indazolyl 11-yl) acetonitrile

Reference Example 1 09: (7-ethyl-1H-thieno [2,3—g] indazo-l-yl)

Reference Example 110: (7-isopropyl-1H-thieno [2,3-g] indazole-1yl) acetonitrile

Reference Example 1 1 1: (1- (2-Methyl-2-nitro-1-propyl) -1H-Flo [2,3-g] indazole

Reference Example 1 1 2 1: 1- (1-t-butoxycarbonylazetidine-3-ylmethyl) — difluoro [2,3-g] indazole

Reference Example 1 1 3: 1- (1-t-butoxycarbonylazetidine-1-ylmethyl) -lfi-furo [2,3-g] indazole

Reference Example 1 14: 1- (1-benzylpiperidine-3-ylmethyl) -1H-furo [2,31 g] indazole Reference example 1 1 5: 2— (1 if—pyrazo mouth [4, 3—h] quinoline—1-1yl) aceto nitrile

Reference example 1 1 6

 0.40 g of 6-hydroxy-7-aminoindazole was mixed with 10 ml of ethyl ethyl formate and heated under reflux for 2 hours. After cooling the reaction solution, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 0.31 g of 1-pyrazo opening [3,4-e] benzoxazole.

Reference Example 1 1 7

 In the same manner as in Reference Example 1 16, 7-methyl-1H-pyrazo [3,4-e] benzoxazole was obtained.

Reference example 1 1 8

 Cyclopene [f] indazolu-7-1-1H-one To a solution of 0.20 g of trifluoroacetic acid (2 ml) was added triethylsilane (0.56 ml) under ice-cooling, and the mixture was stirred at room temperature for 14 hours. did. The solvent was distilled off under reduced pressure, the residue was extracted with chloroform, washed with 1 N aqueous sodium hydroxide solution, and the obtained organic layer was dried using anhydrous sodium sulfate. After removing the desiccant, the solvent was distilled off, and the obtained residue was purified by silica gel column chromatography to obtain 0.08 g of 1,5,6,7-tetrahydrocyclopentyl [f] indazole. Was.

Reference Example 1 1 9

5-Ethoxycarbonyl 4-oxo-1,4,5,6,7-tetrahydrobenzo [b] furan 3.0 g of ethanol (50 ml) solution of hydrazine monohydrate was added to a solution of hydrazine monohydrate. Stirred for 14 hours. The solvent was distilled off under reduced pressure, washed with ethyl hexanoacetate, and dried under reduced pressure to obtain 4,5-dihydro-3-hydroxy-1furo [2,3-g] indazole. To a solution of 1.50 g of the obtained compound in 1,4-dioxane (10 ml) and methanol (20 ml) was added diazomethane (2 eQ), and the mixture was stirred at room temperature for 1 hour. Acetic acid was added to the reaction solution until foaming stopped, and the solvent was distilled off under reduced pressure. The residue was extracted with a black hole form, washed with a saturated aqueous solution of sodium hydrogencarbonate, and the obtained organic layer was dried using anhydrous sodium sulfate. After removing the desiccant, the solvent was distilled off, and the resulting residue was purified by silica gel column chromatography to give 4,5-dichlorobenzene. 0.80 g of draw 3-methoxy-1H-furo [2,3-g] indazole was obtained. From this compound, 3-methoxy-1-fifuro [2,3_g] indazole was obtained in the same manner as in Reference Example 60.

 The compounds of Reference Examples 120 and 121 were obtained in the same manner as in Reference Example 1.

Reference Example 120: 7-chloro-1,4-dihydro-1H-thieno [2,3-g] indazole

Reference Example 121: 7 methyl-4,5 dihydro-1H-thieno [2,3-g] indazole

 The compounds of Reference Examples 122 to 124 were obtained in the same manner as in Reference Examples 1 and 60. Reference Example 122 3-Methyl-1H-Flo [2,3-g] Indazole

Reference Example 123 3-Propyl-1 if-Flo [2,3-g] Indazole

Reference Example 124 3-Ethyru-Flo [2,3-g] Indazole

Reference Example 125

 In the same manner as in Reference Examples 21 and 29, 1- (2 azido 3,3,3 trifluoropropyl) -furo [2,3-g] indazole was obtained.

Example 1

Under an argon stream, 0.18 g of lithium aluminum hydride was suspended in 10 ml of tetrahydrofuran. Under ice-cooling, 1.1 (2-azidoethyl) -1,4-dihydrothieno [2 ', 3': 4,5 A solution of 0.56 g of cyclopentyl [1,2_c] pyrazol in tetrahydrofuran (5 ml) was added and stirred for 30 minutes. The reaction mixture was mixed with methanol to decompose excess lithium aluminum hydride, and 0.18 ml of water, 0.18 ml of 15 sodium hydroxide aqueous solution, and 0.54 ml of water were sequentially added and stirred for 30 minutes. Thereafter, anhydrous sodium sulfate and celite were added, and the mixture was further stirred for 30 minutes. The resulting insolubles were removed by celite filtration, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (eluent: formaldehyde methanol == 95/5), and ethanol and ethyl acetate were added. 4N ethyl acetate hydrochloride solution was added to the mixture, and the resulting crystals were collected by filtration, dried under reduced pressure, and dried under reduced pressure to give 2- (1,4 dihydroceno C2 ', 3': 4,5] cyclopentene [1 , 2-c] pyrazole-1_yl) ethylamine hydrochloride in an amount of 0.42 g. The compounds of Examples 2 to 13 were obtained in the same manner as in Example 1.

Example 2: 2- (1,4-dihydrocheno [3,, 2,: 4,5] cyclopentyl [1,2-c] pyrazol-1-yl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) -1,4-dihydrocheno [3 ', 2': 4,5] cyclopenta [1,2-c] pyrazole

Example 3: 2- (4,5-dihydro-1-furo [2,3-g] indazo-1-yl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) -4,5-dihydro-1H-furo [2,3-g] indazole

Example 4: 2- (4,5-dihydro-1H-furo [3,2-g] indazol-1-yl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) —4,5-dihydro—1H—hout [3,2-g] indazole

Example 5: 2- (4,4-Dimethyl-4,5-dihydrofuro [2,3-g] indazo-l-ul 1-peryl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) -4,4-dimethyl-4,5-dihydro-furo [2,3-g] indazole

Example 6: 2 - (4, 5-dihydro - 1 J ¹ / - thieno [2, 3 - g] indazole one route 1 one I le) Echiruamin hydrochloride

 Ingredients: 1 _ (2-azidoethyl) —4,5-dihydro-1 thieno [2,3—g] indazole

Example 7: 2- (l i-furo [2,3-g] indazole-1yl)-1-methylletylamine hydrochloride

 Ingredients: 1- (2-azidopropyl) -1H-furo [2,3-g] indazole Example 8: 1-ethyl-2- (2-furo [2,3-g] indazole-1-yl ) Etilamine hydrochloride

Ingredients: 11- (2-azidobutyl) -1H-furo [2,3-g] indazole Example 9: 1-cyclohexyl-2- (lii-furo [2,3-g] indazole-1yl) ethylamine Hydrochloric acid salt Example 10: 2— (1H—thieno [2,3-g] indazole—11-yl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) -1-H-thieno [2,3-g] indazole Example 1 1: (S) -2 (Iff-Flo [2,3-g] indazole-1 Yl) 1-methylethylamine hydrochloride

 Ingredients: (S) — 1— (2-azidopropyl) — 1 H-Flo [2, 3— g] indazole

Example 12: 2- (1-furo [2,3-g] indazole-1-1 ^^-) 1 1-trifluoromethylethylamine hydrochloride

Example 13 3: 2- (1H-furo [2,3-g] indazole-1yl) cyclohexylamine fumarate

 The compounds of Examples 14 and 15 were obtained in the same manner as in Reference Examples 82, 21, 29 and Example 1.

Example 14: (S) —2- (7-Methoxy-1 H-thieno [2,3-g] indazole-yl-1-yl) -1-methylethylamine fumarate

 Ingredients: 7-Methoxy-1-thieno [2,3-g] indazole and (?) Propylene oxide

Example 15: (S) -2- (7-tert-butyl-1H-thieno [2,3-g] indazole-1-11yl) — 1-methylethylamine hydrochloride

 Ingredients: 7-tert-butyl-1 thieno [2,3-g] indazole and (R) -propylene oxide

Example 16

 In the same manner as in Reference Examples 1, 21, 29, 60 and Example 1, 3-tert-butyl 4-oxo-1,4,5,6,7-tetrahydrobenzo [b] 8-tert-butyl-1H-thieno [2,3-g] indazole-1-yl) ethylamine hydrochloride was obtained.

Example 17

Reference Example 2 2- (7-Methyl-4,5-dihydro-1H-furo [2,3-g] indazoyl-11-yl) was prepared in the same manner as in 1, 29, 60 and Example 1. Etano I 2- (7-Methyl-furo [2,3-g] indazol-11-yl) ethylamine hydrochloride was obtained from toluene.

Example 18

 Reference Example 21 (S) -1-1 (1H-flow)

 [2,3-g] indazo 1-yl) —from 2-propanol (i?)-2- (1ίί-flow [2,3-g] indazo 1-yl) — 1-methylethylamine dihydrochloride was obtained.

Example 19

 Dissolve 0.32 g of 1- (2-azidoethyl)-7-bromo-4,5-dihydro-1 thieno [2,3-g] indazole in 10 ml of tetrahydrofuran and add trifenylphosphine 0.3 1 g was added, and the mixture was stirred at room temperature for 1 hour. Further, 0.31 g of triphenylphosphine was added, and the mixture was heated under reflux for 1 hour. Then, 0.03 g of water was added, and the mixture was heated under reflux for 8 hours. After cooling the reaction solution, the mixture was acidified by adding 1 N hydrochloric acid, and then the solution was separated with a filter form. The obtained aqueous layer was made alkaline with a 40% aqueous sodium hydroxide solution, and extracted with chloroform. The organic layers were combined and dried over anhydrous magnesium sulfate. After the desiccant is removed by filtration, the solvent is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography (eluent: chromate form Z methanol Z saturated aqueous ammonia solution = 20/1 Z0. 1-1 0/1 / 0.1). This was dissolved in 1.5 ml of ethanol, 0.15 ml of a 4 N solution of ethyl acetate in hydrochloric acid was added, and the resulting crystals were collected by filtration and dried under reduced pressure to give 2- (7-bromo-4, 5-Dihydro-1H-thieno [2,3-g] indazo-1-yl) ethylamine hydrochloride 0.16 g was obtained.

 The compounds of Examples 20 to 42 were obtained in the same manner as in Example 19.

Example 20: 2- (7-Promo-1H-thieno [2,3-g] indazole-1yl) ethylamine hydrochloride

 Ingredients: 11- (2-azidoethyl) _ 7-promo 1 H-thieno [2,3-g] indazole

Example 2 1: 2-(8-Methyl-4,5-dihydro-1H-pyrazo [3,4-e]

 [1, 2] benzisoxazole-1-yl) ethylamine hydrochloride

Example 22: 2- (7-methyl-1 fi-pyrazo mouth [3,4-e] benzothiazo- 1-yl) Etilamine hydrochloride

Example 23: (S) -1-Methyl-2- (1-pyrazo-mouth [3,4-e] benzoxazole-11-yl) ethylamine fumarate

Example 24: (S) -1-Methyl-21- (7-methyl-1 pyrazo [3,4-e] benzoxazo-l-l-yl) ethylamine fumarate

Example 25: (S) —1-Methyl-2- (1H—thieno [2,3-g] indazol—11-yl) ethylamine fumarate

 Ingredients: (S) — 1— (2-azidopropyl) 1H—thieno [2, 3—g] indazole

Example 26: (S) —2_ (7-bromo-1H-thieno [2,3-g] indazolyl-11-yl) -1-methylethylamine fumarate

 Ingredients: (S) _1- (2-azidopropyl) 1-7-bromo-1 thieno [2.3-g] indazole

Example 27: (S) — 2— (7-iodo 1 — thieno [2, 3 _g] indazole 1-yl) — 1-methylethylamine fumarate

 Ingredients: (S) — 1 (2-azidopropyl) 1 7 — 1 1 — Thieno [2, 3 — g] indazole

Example 28: (S) -2- (7-Chloro-1H-thieno [2,3-g] indazo-l-l-yl) _1-methylethylethylamine fumarate

Ingredients: (S) — 1— (2-azidopropyl) 1 7—black mouth— 1 ¹ / —thieno [2,3-g] indazole

Example 29: 2- (7-methyl-1H-thieno [2,3-g] indazole-1yl) ethylamine fumarate

 Ingredients: 1- (2-azidoethyl) -17-methyl-1H-thieno [2,3-g] indazole

Example 30: (S) -1-Methyl-2- (7-methyl-1H-cheno [2,3-g] indazo-1-yl) ethylamine fumarate

Ingredients: (S) — 1— (2-azidopropyl) 1 7-methyl — thieno [2,3-g] indazole Example 31 1: (S) -2- (7-ethyl-1 thieno [2,3-g] indazole-1-yl) — 1-methylethylamine fumarate

 Ingredients: (S) — 1- (2-azidopropyl) 1 7-ethyl-1 p-thieno [2,3-g] indazole

Example 32: (S) -1-Methyl-2- (7-methyl-1H-furo [2,3-g] indazole-1-yl) ethylamine fumarate

 Ingredients: (S) — 11 (2-azidopropyl) 1 7-methyl-1 fi-furo [2,3-g] indazole

Example 33: (S) — 2— (7-isopropyl-1 —thieno [2,3—g] indazole-1yl) — 1-methylethylamine fumarate

 Ingredients: (S) -1-1 (2-azidopropyl) -17-isopropyl-1H-thieno

[2,3—g] indazole

Example 34: 2- (7-Ethoxy-thieno [2,3-g] indazole-1-yl) ethylamine hydrochloride

 Ingredients: 1-1 (2-azidoethyl) 1 7-ethoxy 1 thieno [2,3-g] indazole

Example 35: (S) —2— (3-ethyl-1H—furo [2,3-g] indazole—1-1yl) —1-methylethylamine dihydrochloride

 Ingredients: (S) — 1— (2-azidopropyl) _ 3—ethyl 1 H—furo [2,3-g] indazole

Example 36: (S) -1-Methyl-2- (3-propyl-1f-fluoro [2,3-g] indazo-1-yl) ethylamine dihydrochloride

 Ingredients: (S) — 1— (2-azidopropyl) — 3-propyl— 1 H—furo [2,3-g] indazole

Example 37: (5) —2- (3-Methoxy-1-H-furo [2,3-g] indazole—1-yl) -1-methylethylamine fumarate

 Ingredients: (S) — 1— (2-azidopropyl) — 3-methoxy— 1 H—furo [2,3-g] indazole

Example 38: 2- (7-node-4,5-dihydro-1 1-thieno [2,3_g] Indazo 1-ethyl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) — 7-odo-4,5-dihydro-1H—Ceno [2,3-g] indazole

Example 3 9: 2- (7-hydroxy 1 H-thieno [2,3-g] indazol-11-yl) ethylamine hydrochloride

 Ingredients: 1— (2-azidoethyl) —7-hydroxy 1 H—thieno [2,3—g]

Example 40: 2- (8-Methyl-pyrazo [3,4-e] [1,2] benzisoxazole-1-yl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) 8-methyl-1H-pyrazo mouth [3,4-e] [1,2] benzisoxazole

Example 4 1: 2- (7-Methoxy-4,5-dihydro-1H-thieno [2,3-g] indazol-1-yl) ethylamine hydrochloride

 Ingredients: 11- (2-azidoethyl) -17-methoxy-4,5-dihydro-1H-thieno [2,3-g] indazole

Example 42: 2- (7-chloro-1,4,5-dihydro-1H-thieno [2,3_g] indazo-1-yl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) -17-chloro-4,5-dihydro-1H-cheno [2,3-g] obtained from indazole.

Example 43

[2-Flo [2,3-g] indazol-1-yl) ethyl] acetamide 0.5 1 g of ethylene glycol (20 ml) solution, add 1.60 g of potassium hydroxide and add 1700 ° The mixture was stirred at C for 2 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layers were combined, washed with water and saturated saline, and then dried over anhydrous magnesium sulfate. After the desiccant was removed by filtration, the filtrate was concentrated, and the obtained residue was purified by silica gel column chromatography (eluent: chloroform-form Z methanol = 95/5) to give 2- (Ifflo [2, 3—g] Indazole-11-yl) Echilamine was obtained. The obtained 2- (1H-furo [2,3-g] indazole-1-yl) ethylamine was dissolved in a mixed solvent of ethanol and ethyl acetate, and a 4N ethyl acetate hydrochloride solution was added thereto. The resulting crystals were collected by filtration and dried under reduced pressure to obtain 0.06 g of 2- (1H-furo [2,3-g] indazole-1-yl) ethylamine hydrochloride.

Example 44

 ON- [2- (4,5-dihydro-1H-furo [3,2-g] indazol-1-yl) ethyl] acetamide from Reference Example 60 and Example 43 Furo [3,2-g] indazole (1 ^^^) ethylamine hydrochloride was obtained.

 The compounds of Examples 45 and 46 were obtained in the same manner as in Reference Example 29 and Example 1.

Example 45: 1— (lfi-furo [2,3—g] indazole-1-ylmethyl) butyramine hydrochloride

Example 46: 1- (1H-furo [2,3-g] indazol-1-ylmethyl) -1-2-methylpropylamine hydrochloride

 The compounds of Examples 47 and 48 were obtained in the same manner as in Reference Example 60 and Example 19.

Example 47: 2- (7-Methoxy-1H-cheno [2,3-g] indazole-1-yl) ethylamine hydrochloride

 Ingredients: 1- (2-azidoethyl) _7-methoxy-4,5-dihydro-thieno [2,3-g] indazole

Example 48: 2- (7-Chloro-1H-thieno [2,3-g] indazo-l-yl) ethylamine hydrochloride

 Ingredients: 11- (2-azidoethyl) -17-chloro-4,5-dihydro-1H-cheno [2,3-g] indazole

Example 49

 2- (1H-thieno [2,3-g] indole-11-yl) ethylamine was obtained in the same manner as in Example 43.

 The compounds of Examples 50 to 55 were obtained in the same manner as in Example 1.

Example 50: 2- (1H-furo [2,3-g] indazole-1_yl) propylamine hydrochloride Ingredients: 2— (If-Flo [2,3-g] Indazo-1-yl) Propionit Example 5 1: 2-(1 J —Pyrazo Mouth [4,3-h] Quinoline-11-yl ) Ethylamine fumarate

 Ingredients: 2— (1 H—pyrazo mouth [4,3—h] quinoline—11-yl) acetonitrile

Example 5 2: 2— (1,5,6,7-tetrahydrocyclopenta [f] indazole—one-yl) ethylamine dihydrochloride

Example 5 3: 2- (7-ethyl-1H-thieno [2,3-g] indazol-1-yl) ethylamine fumarate

 Ingredients: (7-ethyl-1-thieno [2,3-g] indazo-one-one-one)

Example 54: 2- (7-isopropyl-1H-thieno [2,3-g] indazole-1-yl) ethylamine fumarate

 Ingredients: (7-isopropyl-1-H-thieno [2,3-g] indazole-11-yl) acetonitrile

Example 5 5: 2-(3-Ethyru-furo [2,3-g] indazolu 1-yl) Echiluamine dihydrochloride

 Ingredients: 2- (3-ethyl-1H-furo [2,3-g] indazole-1-yl) acetonitrile

Reference Example 79 The compounds of Examples 56 and 57 were obtained in the same manner as in Example 9 and Example _c. Example 56: 2- (7,8-dihydro-1H-furo [2,3-g] indazole — 1-yl) ethylamine fumarate

 Ingredients: 7,8-dihydro-1H-furo [2,3-g] indazole

Example 5 7: 2- (7-tert-butyl-1H-thieno [2,3-g] indazole-1-yl) ethylamine hydrochloride

 Ingredients: 7-tert-butyl-1 fi-thieno [2,3—g] indazole

Example 5 8

In the same manner as in Reference Example 9, the 3-methyl-1 flow [2,3-g] (S) — 1-Benzyloxycarbonyl 2- (3-methyl — 1 H— from Zol and (S) —methyl (1-benzyloxycarbonylpyrrolidine-1-yl) methanesulfonate Furo [2,3-g] indazole-1-ylmethyl) pyrrolidine was obtained. This was dissolved in ethanol (2 Om 1), 0.06 g of 10% palladium-carbon was added, and the mixture was stirred at room temperature for 12 hours under a hydrogen atmosphere at normal pressure. The reaction mixture was filtered using celite, and the solvent was distilled off under reduced pressure. 3 ml of methanol was added to the resulting residue to dissolve it, and 5 ml of ether was added.The resulting precipitate was collected by filtration, dried under reduced pressure, dissolved in 5 ml of methanol, and dissolved in 1 ml of 4 N ethyl acetate hydrochloride. l, and the solvent was distilled off. After that, methanol was added to the obtained residue to dissolve it. Ether was added, and the resulting precipitate was collected by filtration, dried under reduced pressure, and dried under reduced pressure to give (S) _3-methyl-1- ( Pyrrolidine-2-ylmethyl)-Iff-Flo

 [2,3-g] Indazole dihydrochloride 0.17 g was obtained.

 The compounds of Examples 59 to 62 were obtained in the same manner as in Example 58.

Example 59: (S) -3-Ethyl-1- (pyrrolidine-2-ylmethyl) -1-H-furo [2,3-g] indazole hydrochloride

Example 6 0 1-[(R) — 2-pyrrolidinylmethyl] — —furo [2,3 — g] indazole dihydrochloride

 Ingredients: —Flo [2,3-g] indazole and (i?)-1- (1-benzyloxy-proponylpyrrolidine-1-yl) methyl methanesulfonate

Example 6 1: 1 — [(S) -1-2-pyrrolidinylmethyl] —— furo [2,3-g] indazole dihydrochloride

 Ingredients: Iff-furo [2,3-g] indazole and (S)-(1-benzyloxykarponylpyrrolidine-2-yl) methyl methanesulfonate

Example 6 2: 1- (2-piperidylmethyl) -1H-furo [2,3-g] indazole hydrochloride

Example 6 3

1- (2-Methyl-2-nitro-1-propyl) 1-furo [2,3-g] indazole 0.37 g of methanol (1 Om 1), 0.04 g of platinum oxide, and water The mixture was stirred at room temperature for 24 hours under a hydrogen atmosphere. The reaction solution was filtered using celite, and the solvent was distilled off under reduced pressure. The residue obtained is purified by silica gel column chromatography (elution Liquid: Black-mouthed form Z Methanol Z Saturated aqueous ammonia = 100X10 / 1) Purified by treatment with 4N ethyl acetate hydrochloride solution in methanol Z ethyl acetate 0.1

4 g of 2-furo [2,3-g] indazole-1-yl) -1, 1 -dimethylmethyluamine dihydrochloride was obtained.

Example 64

 2-(1H-Flo [2,3-g] Indazole-11-yl)

50 g was dissolved in 10 ml of ethanol, and 0.43 g of hydroxylamine hydrochloride and 2 ml of pyridine were added thereto, followed by heating under reflux for 1 hour. After cooling the reaction solution, the solvent was concentrated under reduced pressure, and this was dissolved in chloroform. This was washed with water and a saturated aqueous solution of sodium chloride, and then dried over magnesium sulfate. After removing the drying agent by filtration, the solvent was concentrated under reduced pressure, and the residue was recrystallized from a mixed solvent of acetic acid-form-form. From this compound, 2- (1H-fluoro) having a diastereomer ratio of about 7: 3 was obtained in the same manner as in Example 1.

[2,3-g] Indazoyl 11-yl) Cyclopentylamine fumarate was obtained.

Example 65

 By a method similar to that in Example 64, 2- (1H-furo [2,3-g] indazole-1-yl) -11-phenylethylamine 0.5 fumarate was obtained.

Example 66

 1- (1-t-butoxycarbonylazetidine-1-3-ylmethyl) -1H-furo [2,3-g] indazole 0.46 g of ethyl acetate (1 Om 1) solution in 4N ethyl acetate hydrochloride acetate (3 ml) was added and the mixture was stirred at room temperature for 4 hours. After evaporating the solvent under reduced pressure, the residue was extracted with chloroform and washed with 1N sodium hydroxide, and the obtained organic layer was dried using anhydrous sodium sulfate. After removing the desiccant, the solvent is distilled off, and the residue obtained is purified by silica gel column chromatography (eluent: hexane Z ethyl acetate = 5 Z 1) and treated with fumaric acid in methanol Z ethyl acetate. As a result, 0.19 g of 2-chloromethyl-3- (1H-furo [2,3-g] indazo-1-yl) propylamine fumarate was obtained.

The compounds of Examples 67 and 68 were obtained in the same manner as in Example 66.

Example 67: 1- (azetidine-l-2-ylmethyl) -— furo [2,3-g] in Dazol dihydrochloride

 Ingredients: 1- (1-t-butoxycarbonylazetidine-l-ylmethyl) 1-1H-furo [2,3-g] indazole

Example 68: 1- (azetidine-3-ylmethyl) -iff-furo [2,3-g] indazole fumarate

 Ingredients: 1- (1-t-butoxycarbonylazetidine-3-ylmethyl) 1-H-fluoro [2,3-g] indazole

Example 69

 In the same manner as in Reference Examples 1 and 60 and Example 1, 1- (one-one) was obtained from 4-oxo-1,4,5,6,7-tetrahydrobenzo [b] furan and 3-hydrazino-11-benzoylpyrrolidine. 1- (Pyrrolidine-13-yl) 1-1H-furo [2,3-g] indazol hydrochloride was obtained from benzoylol 3-pyrrolidinyl) furo [2,3-g] indazole.

Example 70

 1- (1-Benzylpiperidine-3-ylmethyl) -lfi-furo [2,3-g] indazole To 0.17 g of dichloroethane (20 ml) solution was added 2-chloroethylchloroformate (0.15 ml). The mixture was stirred for 13 hours under heating and reflux, and then methanol (20 ml) was added. The mixture was further stirred for 3 hours under heating and reflux. After evaporating the solvent under reduced pressure, the residue was dissolved in 1N aqueous hydrochloric acid and washed with ethyl acetate. The resulting hydrochloric acid extract was made basic with potassium carbonate and extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate. After removing the desiccant, the solvent was distilled off, and the resulting residue was purified by silica gel column chromatography (eluent: chromatoform Z methanol / saturated aqueous ammonia = 100 ノ 10Z1), and this was purified in methanol / ethyl acetate. To give 0.053 1- (3-piperidylmethyl) 1-1H-furo [2,3-g] indazole dihydrochloride.

Example 71

2- (7-Acetylamino-lfi-thieno [2,3-g] indazole-1-yl) ethylamine hydrochloride was obtained in the same manner as in Reference Examples 1, 21, 29, 60 and Example 1. . The chemical structural formulas and physicochemical properties of the compounds obtained in Reference Examples and Examples are shown in the following table.

 The symbols in the table have the following meanings.

 Rf .: Reference example number

Ex .: Example number

NMR: nuclear magnetic resonance spectrum (unless otherwise specified DMSO-d _6, TMS internal standard) δ: m / z: Mass spectrometry value (m / z)

Me: methyl group

Et: ethyl group

Table 2-1

 Rf.

 NMR: 2.70-2.76 (2H, m), 2.90-2.96 (2H, m), 3.72-3.78 (2H, m), 4.32 (2H, t), 4.93 (IH, t),

1

 7.30 (lH, s), 7.46 (lH, d), 7.49 (lH, d)

_{NMR (CDC 1 3): 3.25} (IH, t), 3. 5 (2H, s), 4.06-4.11 (2H, m), 4.30-4.38 (2H, m), 7.11 (IH,

Two

 d), 7.28 (lH, d), 7.42 (lH, s)

 NMR (CDC): 2.89-2.95 (4H, m), 4.06 (2H, t), 4.32 (2H, t), 6.58 (IH, d), 7.29 (IH, s), 7.37

Three

 (IH, d)

_{NMR (CDC 1 3): 2.78-2.81} (4H, m), 4.05 (2H, t), 4.50 (2H, t), 6.39 (IH, d), 7.30 (1H, s), 7.37

Four

 (IH, d)

_{NMR (CDC 1 3): 1.29} (6H, s), 2.75 (2H, s), 4.06 (2H, t), 4.32 (2H, t), 6.59 (IH, d), 7.32 (1H,

Five

 s), 7.38 (lH, d)

 NMR (CDC): 3.28 (1H, t), 3.59 (2H, s), 4.06-4.11 (2H, m), 4.39-4.43 (2H, m), 7.15 (1H,

6

 d), 7.34 (lH, d), 7.39 (lH, s)

_{NMR (CDC 1 3): 2.77-2.85} (2H, m), 2.85-2.93 (2H, m), 3.40-3.50 (1H, m), 4.05-4.15 (2H, m),

7

 4.34-4.40 (2H, m), 7.25 (1H, s), 7.34 (IH, s)

_{NMR (CDC1 3): 2.76-2.85 (} 2H, m), 2.90-2.98 (2H, m), 3.38-3.53 (1H, brs), 4.05-4.15 (2H,

8

 m), 4.35—4.41 (2H, m), 7.34 (IH, s), 1.41 (IH, s)

 NMR (CDCI3): 2.78-2.85 (2H, m), 2.85-2.93 (2H, m), 3.38 (IH, t), 4.06-4.15 (2H, m), 4.33-

9

 4.39 (2H, m), 7.12 (lH, s), 7.34 (lH, s)

_{NMR (CDC 1 3): 2.77-2.84} (4H, m), 3.91 (3H, s), 4.04-4.12 (2H, m), 4.33-4.40 (2H, m), 6.40

Ten

 (1H, S), 7.30 (1H, S)

 NMR (CDC): 2.57 (3H, s), 1.83-2.89 (2H, m), 2.96-3.02 (2H, m), 3.51 (1H, t), 4.08

11

 (2H, q), 4.39 (2H, t), 7.37 (IH, s)

_{NMR (CDC 1 3): 2.71} (3H, s), 2.87 (2H, t), 3.00 (2H, t), 4.05 (. 2H t), 4.75 (2H, t), 7.33

12

 (lH.s)

 13 NMR (CDCI3): 2.84-2.91 (2H, m), 2.94-3.01 (2H, m), 7.33 (IH, m), 7.51 (IH, s)

_{14 NMR (CDC 1 3):} 2.87-2.92 (4H, m), 7.31 (1H, s), 7.33 (1H, s)

_{NMR (CDC 1 3): 2.49} (3H, s), 2.76-2.92 (4H, m), 4.08 (2H, t), 4.40 (2H, t), 6.92 (IH, s),

Fifteen

 7.31 (lH, s)

_{16 NMR (CDC 1 3):} 1.32 (3H, t), 2.79-2.98 (6H, m), 7.05 (1H, s), 7.32 (1H, s)

 NMR: 2.29 (3H, s), 2.74-2.85 (4H, m), 3.65-3.75 (2H, m), 4.14-4.20 (2H, m), 6.48 (IH,

17

 s), 7.20 (lH, s)

 18 NMR: 2.27 (3H, s), 2.77-2.82 (4H, m), 6.23 (1H, s), 7.40 (IH, s), 12.20 (1H, rs)

_{NMR (CDC 1 3): 1.34} (6H, d), 2.85-2.99 (2H, m), 3.07-3.18 (IH, m), 7.06 (IH, s), 7.31

19

 (lH, s)

 NMR: 1.35 (3H, t), 2.66-2.77 (4H, m), 3.69-3.76 (2H, m), 4.13 (2H, q), 4.23-4.28 (2H,

20

 m), 4.90 (lH, t), 6.70 (lH, s), 7.25 (lH, s)

 NMR (CDCI3): 2.74 (3H, s), 3.59 (2H, s), 4.59-4.69 (4H, m), 7.21 (IH, d), 7.35 (1H, d), 7.41

twenty one

 (IH, s)

_{NMR (CDC 1 3): 2.77} (3H, s), 3.45 (2H, s), 4.54-4.59 (2H, m), 4.65-4.69 (2H, m), 7.11 (1H,

twenty two

 d), 7.29 (lH, d), 7.44 (lH, s)

_{NMR (CDC 1 3): 2.78} (3H, s), 2.88-2.93 (4H, m), 4.53 (2H, t), 4.64 (2H, t), 6.64 (IH, d), 7.33

twenty three

(1H, S), 7.38 (1H, d)

Table 2—4

 Rf.

_{67 NMR (CDC 1 3):} 7.45 (1H, dd), 7.62 (IH, d), 7.67 (1H, d), 8.08 (IH, s)

 NMR (CDC "): 2.68 (3H, s), 3.84 (2H, t), 4.80 (2H, t), 7.38 (1H, s), 7.50 (IH, d), 7.55

68

 (1H, d), 8.06 (1H, s)

_{69 NMR (CDC 1 3):} 2.67 (3H, s), 7.28 (IH, s), 7.52 (1H, d), 7.59 (IH, d), 8.14 (1H, s)

 NMR (CDC): 1.43 (3H, t), 3.02 (2H, q), 7.31 (IH, s), 7.53 (IH, d), 7.60 (IH, d), 8.14

70

 (lH, s)

 NMR: 2.51 (3H, s), 6.76-6.79 (IH, m), 7.28-7.34 (IH, m), 7.52-7.57 (IH, m), 8.07-

71

 8.10 (lH, m), 13.29 (lH, brs)

 NMR (CDC): 1.44 (6H, d), 3.27-3.36 (1H, m), 7.33 (IH, s), 7.52 (IH, d), 7.59 (IH, d),

72

 8.15 (lH, s)

丽_{R (CDC1 3): 1.52 (} 3H, t), 3.81-3.86 (2H, m), 4.29 (2H, q), 4.75-4.80 (2H, m), 6.80-

73

 6.82 (1H, m), 7.37-7.41 (1H, m) '7.51 (IH, d), 8.05 (1H, s)

_{NMR (CDC 1 3): 1.87} (3H, s), 3.79-3.85 (2H, m), 4.69-4.73 (2H, m), 5.92 (IH, brs), 7.24 (1H,

74

 dd), 7.38 (IH, dd), 7.58 (IH, d), 7.74 (IH, d), 8.06 (IH, s)

_{NMR (CDC 1 3): 4.03} ((3H, s), 6.91 (1H, s), 7.44 (IH, d), 7.55 (IH, d), 8.08 (1H, d),

75

 13.31-13.40 (lH, brs)

_{76 NMR (CDC 1 3):} 1.50 (9H, s), 7.34 (IH, s), 7.54 (1H, d), 7.60 (1H, d), 8.14 (IH, s)

_{NMR (CDC 1 3): 1.91} (3H, s), 2.89-2.92 (4H, m), 3.72 (2H, t), 4.34 (2H, t), 6.67 (IH, d), 7.31

77

 (1H, S), 7.37 (1H, d)

_{NMR (CDC 1 3): 1.91} (3H, s), 2.79 (4H, t), 3.71-3.76 (2H, m), 4.46-4.50 (2H, m), 6.23 (IH,

78

 brs), 6.39 (IH, d), 7.30 (IH, s), 7.38 (IH, d)

_{NMR (CDC 1 3): 1.25} (3H, t), 4.23 (2H, q), 5.33 (2H, s), 6.95 (1H, dd), 7.40 (IH, dd), 7.61

79

 (IH, d), 7.73 (lH, d), 8.08 (IH, s)

_{NMR (CDC1 3): 3.01 (} IH, t), 4.18-4.23 (2H, m), 4.68-4.71 (2H, m), 7.11 (IH, dd), 7.39 (IH,

80

 dd), 7.60 (IH, d), 7.75 (1H, d), 8.06 (IH, s)

 NMR: 5.67 (2H, s), 7.40-7.42 (IH, m), 7.46 (IH, d), 7.68 (IH, d), 8.08-8.10 (1H, m), 8.18

81

 (1H, S), 9.79 (1H, S)

_{NMR (CDC 1 3): 1.33} (3H, d), 3.30 (1H, d), 4.41-4.63 (3H, m), T.11 (1H, d), 7.39 (IH, d), 7.60

82

 (IH, d), 7.75 (lH, d), 8.07 (IH, s)

 NMR: 1.05 (3H, d), 4.20-4.33 (1H, m), 4.52-4.61 (IH, m), 4.63-4.74 (IH, m), 4.92 (IH,

83

 d), 7.56 (1H, d), 7.80 (IH, d), 8.21 (IH, s), 8.87 (1H, s)

 NMR: 1.03 (3H, d), 2.65 (3H, s), 4.20-4.30 (IH, m), 4.48-4.56 (IH, m), 4.60-4.70 (IH,

84

 m), 4.90 (1H, d), 7.46 (IH, d), 7.70 (IH, d), 8.17 (1H, s)

 NMR: 1.10 (3H, d), 4.03-4.17 (1H, m), 4.45-4.56 (IH, m), 4.60-4.73 (IH, m), 4.99 (IH,

85

 d), 7.67-7.71 (2H, m), 7.88-7.92 (1H, m), 8.01-8.05 (IH, m), 8.12 (IH, s)

_{NMR (CDC 1 3): 1.37} (3H, d), 4.49-4.67 (3H, m), 7.47 (IH, dd), 7.64 (1H, d), 7.78 (IH,

86

 d), 8.07 (lH, s)

 NMR: 1.10 (3H, d), 4.03-4.15 (IH, m), 4.43-4.54 (1H, m), 4.60-4.70 (IH, m), 5.00 (1H,

87

 d), 7.63-7.67 (2H, m), 8.12 (IH, s), 8.27 (1H, s)

_{NMR (CDC 1 3): 1.35} (3H, d), 4.38-4.63 (3H, m), 7.43 (IH, d), 7.59-7.64 (2H, m), 8.04

88

(lH, s) Table 2-5

 Rf.

_{NMR (CDC 1 3): 1.35} (3H, d), 2.69 (3H, s), 4.41-4.59 (2H, m), 4.68 (1H, dd), 7.43 (IH, s),

89

 7.50 (1H, d), 7.56 (lH, d), 8.04 (IH, s)

_{NMR (CDC 1 3): 1.35} (3H, d), 1.43 (3H, t), 3.04 (2H, q), 4.46-4.60 (2H, m), 4.69 (2H, dd),

90

 7.45 (IH, s), 7.51 (IH, d), 7.56 (IH, d), 8.05 (IH, s)

 NMR: 1.08 (3H, d), 2.51 (3H, s), 3.98-4.0 (1H, m), 4.25-4.60 (2H, m), 4.93 (IH, d),

91

 7.03-7.08 (1H, m), 7.28-7.36 (IH, m), 7.49-7.56 (IH, m), 8.06 (IH, s)

_{NMR (CDC1 3): 1.35 (} 3H, d), 1.45 (6H, d), 3.41-3.32 (1H, m), 4.60-4.47 (2H, m), 4.69

92

 (IH, dd), 7.45 (IH, s), 7.52 (IH, d), 7.57 (IH, d), 8.04 (1H, s)

_{NMR (CDC 1 3): 1.29} (3H, d), 4.09 (3H, s), 4.20-4.43 (3H, m), 7.01 (IH, dd), 7.27 (1H,

93

 dd), 7.51 (IH, d), 7.70 (1H, d)

 NMR (CDCI3): 1.33 (3H, d), 4.40-4.45 (IH, m), 4.47-4.52 (lH, m), 4.56-4.64 (IH, m),

94 7.08-7.12 (lH, m), 7.36-7.41 (IH, m), 7.60 (IH, d), 7.73-7.78 (IH, i), 8.07

 (lH, s)

 NMR: 4.45-4.56 (1H, m), 4.70-4.90 (2H, m), 6.68 (IH, d), 7.34-7.38 (1H, m), 7.44

95

 (IH, d), 7.64 (lH, d), 8.10-8.15 (1H, m), 8.19 (lH, s)

 NMR: 1.35.210 (8H, m), 3.88-4.00 (1H, m), 4.40-4.55 (IH, m), 4.65 (IH, d), 7.36-

96

 7.41 (IH, m), 7.44-7.48 (IH,), 7.61 (IH, d), 8.05-8.08 (IH, m), 8.11 (IH, s)

NMR (CDCI3): 1.29 (3H, d), 1.41 (3H, t), 3.00 (2H, q), 4.32-4.42 (2H, m), 4.47-4.55

97

 (IH, m), 7.06 (IH, dd), 7.33 (1H, dd), 7.53 (IH, d), 7.72 (1H, d)

 NMR: 1.32 (3H, d), 4.15-4.22 (1H, m), 4.60-4.78 (2H, m), 7.44-7.48 (IH, m) '7.50-7.58

98

 (lH, m), 7.67 (m, d), 8.13 (1H, d), 8.19 (1H, s)

_{NMR (CDC 1 3): 1.05} (3H, t), 1.54-1.66 (2H, m), 3.37 (IH, brs), 4.07-4.15 (IH, m), 4.46 (IH,

99 dd), 4.61 (IH, dd), 7.08-7.10 (1H, m), 7.37 (1H, d), 7.57 (1H, d), 7.73 (1H, d), 8.04 (lH, s)

_{NMR (CDC 1 3): 0.95} (3H, t), 1.38-1.66 (4H, m), 3.36 (IH, brs), 4.16-4.22 (lH, m), 4.45 (IH,

100 dd), 4.59 (IH, dd), 7.09 (1H, dd), 7.37 (IH, dd), 7.57 (1H, d), 7.72 (IH, d), 8.03 (IH, s)

_{NMR (CDC 1 3): 1.09} (3H, t), 1 · 82-1.93 (IH, m), 3.21 (1H, d), 3.91-3.96 (IH, m), 4.51 (1H,

101 dd), 4.69 (1H, dd), 7.10 (1H, dd), 7.38 (IH, dd), 7.60 (IH, d), 7.74 (1H, d), 8.07 (1H, dd)

 s)

_{NMR (CDC 1 3): 1.09-2.03} (10H, m), 3.27 (IH, d), 3.56-3.63 (IH, m), 3.90-3.95 (IH, d), 4.48

102 (1H, dd), 4.66 (1H, dd), 7.09 (1H, dd), 7.36 (IH, dd), 7.57 (1H, d), 7.72 (IH, d), 8.02

 (lH, s)

_{NMR (CDC 1 3): 1.88} (3H, s), 3.68-3.74 (2H, m), 4.62 (2H, t), 5.35-5.47 (IH, brm), 6.63 (IH,

103

 d), 7.02 (1H, d), 7.53 (IH, d), 7.61 (2H, s), 7.78 (1H, s)

 NMR: l.94 (3H, d), 6.46 (IH, q), 7.56 (IH, dd), 7.67 (IH, dd), 7.74 (1H, d), 8.20 (IH, d),

104

 8.33 (lH, s)

 NMR: 6.33 (2H, s), 7.16-7. L7 (lH, m), 7.46 (IH, d), 7.59-7.64 (2H, m), 7.69 (IH, d),

105

 7.71-7.77 (1H, m), 8.00-8.02 (IH, m), 8.14 (2H, m), 8.18 (IH, s)

 NMR: 1.80-2.60 (6H, m), 5.60 (IH, t), 7.46 (IH, d), 7.51-7.53 (IH, m), 7.66 (IH, d),

106

8.09-8.1K1H, m), 8.16 (lH, s) Table 2—6

 Rf.

_{NMR (CDC 1 3): 1.42} (3H, t), 3.01 (2H, q), 5.41 (2H, s), 7.13 (1H, d), 7.43 (IH, d), 7.57

107

 (1H, d), 7.79 (lH, d),

_{NMR (CDC 1 3): 2.11-2.21} (2H, m), 2.96-3.06 (4H, m), 5.25 (2H, s), 7. 8 (1H, s), 7.52

108

 (1H, S), 7.95 (1H, S)

_{NMR (CDC 1 3): 1.45} (3H, t), 3.06 (2H, q), 5.57 (2H, s), 7.45 (IH, s), 7.56 (IH, d), 7.60

109

 (IH, d), 8.08 (lH, s)

_{NMR (CDC 1 3): 1.47} (6H, d), 3.34-3.43 (IH, m), 5.58 (2H, s), 7.45 (IH, s), 7.57 (IH, d),

110

 7.6K1H, d), 8.08 (lH, s)

_{NMR (CDC 1 3): 1.68} (6H, s), 5.04 (2H, s), 7.12 (1H, dd), 7.40 (IH, d), 7.59 (IH, d), 7.76

111

 (IH, d), 8.08 (lH, s)

_{NMR (CDC 1 3): 1.43} (9H, s), 3.18-3.28 (1H, m), 3.85 (2H, dd), 4.04 (2H, t), 7.07 (IH,

112

 dd), 7.38 (IH, dd), 7.69 (IH, d), 7.76 (IH, d), 8.03 (1H, s)

 NMR (80 ° C): 1.6 (9H, s), 2.05-2.28 (2H, m), 3.74-3.59 (2H, m), 4.57-4.63 (1H, m),

113 4.76 (IH, dd), 4.89 (1H, dd), 7.34 (IH, dd), 7.45 (IH, dd), 7.62 (IH, d), 8.03 (1H, d), 8.09 (lH, s )

_{NMR (CDC 1 3): 1.50-1.65} (4H, m), 2.00-2.07 (2H, m), 2.40 (1H, br), 2.61-2.72 (2H, m),

114 3.40 (1H, d), 3.47 (IH, d), 4.48 (2H, d), 7.05 (IH, dd), 7.21-7.29 (5H, m), 7.35

 (IH, dd), 7.57 (1H, d), 7.73 (IH, d), 8.01 (IH, s)

_{NMR (CDC 1 3): 6.29} (2H, s), 7.51 (1H, d), 7.55 (IH, dd), 7.76 (1H, d), 8.18 (IH, s), 8.28

115

 (IH, dd), 8.95 (lH, dd)

 116 NMR: 7.55 (1H, d), 7.82 (IH, d), 8.23 (1H, s), 8.83 (1H, s), 13.85 (1H, brs)

 117 NMR: 2.69 (3H, s), 7.45 (IH, d), 7.71 (1H, d), 8.18 (1H, s), 13.72 (1H, brs)

_{NMR (CDC 1 3): 2.05-2.91} (2H, m), 2.95-3.02 (4H, m), 7.30 (IH, s), 7.52 (IH, s), 7.96

118

 (lH, s)

 119 NMR: 4.01 (3H, s), 7.09 (1H, d), 7.29 (IH, d), 7.45 (1H, d), 8.03 (IH, d)

_{120 NMR (CDC1 3): 2.86-2.94} (4H, m), 7.18 (IH, s), 7.33 (IH, s)

_{121 NMR (CDC 1 3):} 2.48 (3H, s), 2.84-2.97 (4H, m), 7.00 (IH, s), 7.32 (IH, s)

_{122 NMR (CDC 1 3):} 2.63 (3H, s), 6.98 (1H, d), 7.37 (1H, d), 7.54 (IH, d), 7.71 (IH, d)

_{NMR (CDC 1 3): 1.03} (3H, t), 1.82-1.95 (2H, m), 3.00 (2H, t), 6.98 (IH, dd), 7.36 (IH,

one two Three

 dd), 7.57 (lH, d), 7.70 (lH, d)

_{NMR (CDC 1 3): 1.45} (3H, t), 3.06 (2H, q), 6.98 (1H, dd), 7.36 (IH, dd), 7.57 (IH, d), 7.70

124

 (1H, d)

 NMR: 4.78-4.88 (1H, m), 5.02-5.06 (IH, m), 5.28-5.43 (IH, m), 7.38-7.42 (IH, m),

125

7.50 (1H, d), 7.70 (IH, d), 8.13-8.16 (IH, m), 8.27 (IH, s) Table 3

Claims

The scope of the claims

1. A tricyclic pyrrole or pyrazole derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof.

 (The symbols in the formula have the following meanings

Y ring: an unsaturated 5-membered ring which may have 1 to 3 or 1 or 3 or more hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, or 1 to 2 nitrogen atoms Unsaturated 6-membered ring

 X: bond or carbon atom

 -: Double bond or single bond

 V: nitrogen atom or group represented by formula CH

 A: A linear or branched lower alkylene group which may be substituted with an octogen atom or a cycloalkyl group

R ¹ and R ^2: the same or different and represent a hydrogen atom, a lower alkyl group or R ¹ and R ² or A is may be formed hetero ring together with the adjacent nitrogen atom a nitrogen-containing saturated R ³ and R ⁴ : Same or different hydrogen atom, lower alkyl group, hydroxyl group, lower alkoxy group, amino group, mono- or di-lower alkylamino group, lower alkanoylamino group or halogen atom

R ^{5 to} R ⁹ : the same or different, a hydrogen atom, a lower alkyl group, a hydroxyl group or a lower alkoxy group

However, when: τττ is a double bond, R ⁶ and R ⁸ do not exist. Also, when X is a bond,: 7 is a single bond and R ⁷ and R ⁸ are absent. )

Claim 1 which is 2.

A compound as described.

 3. The compound according to claim 2, wherein A is an ethylene or propylene group.

 4. The compound according to claim 3, wherein the Y ring is a furan or thione: n ring.

 5.2-(lfi-flow [2,3-g] indazole-1 ^^^) ethylamine, 2 ^ (7-bromo-1Ji-thieno [2,3-g] indazole-1 $ ) Ethiluamine, 2— (7—Ed—1 Jf-thieno [2,3—g] Indazo 1 11) Echilamine, 2— (7—Methoxy—1 thieno [2,3—g] Indazo 1 1-yl) ethylamine, (S) -2- (1H-furo [2,3-g] indazole-1-1-yl) _1-methylethylamine, 2_ (7-methyl-1fi-thieno [2, 3-g] indazole- 1-yl) ethylamine, (S) -2- (7-methoxy-1H-thieno [2,3-g] indazole-1-yl)-1-methylethyla Min,

(S) — 1 _ methyl — 2 — (7 _ methyl — 1 / ί—thieno [2,3-g] indazole — 1 — yl) ethylamine, 2_ (7-ethyl — 1 1—thieno [2, 3 -g] Indazo 1-1) Echilamine, (S)-2-(7-Echil-1-Thieno)

The compound according to claim 4, which is [2,3-g] indazole-1-yl) -1-methylethylamine or a pharmaceutically acceptable salt thereof.

 6. A pharmaceutical composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

7. The pharmaceutical composition according to claim 6, which is a 5-HT _2C agonist.

 8. The pharmaceutical composition according to claim 7, which is a therapeutic agent for impotence.